陆军军医大学学报 (Oct 2022)
Protective effect of dexmedetomidine on intestinal barrier function in septic rats
Abstract
Objective To investigate the protective effect of dexmedetomidine (DEX) on intestinal barrier in septic rats. Methods Rat model of sepsis was induced by cecal ligation and puncture (CLP). SD rats were randomly divided into 4 groups: sham operation group, sepsis group, conventional treatment group and DEX group. The survival rate, survival time and blood levels of pro-inflammatory cytokines (TNF-α and IL-1β), while the intestinal permeability, blood diamine oxidase (DAO) level, pathological morphology of intestinal tissue and polarization of local intestinal macrophages were observed in the rats of different groups. Mouse macrophage line RAW264.7 were divided into control group, lipopolysaccharide (LPS) group and DEX group. The effect of DEX on the polarization of macrophages stimulated by LPS was determined in the cells of 3 groups. Results Compared with the sham group, the septic rats had significantly lower survival rate and shorter survival time (P < 0.01), increased intestinal permeability and levels of pro-inflammatory cytokines (P < 0.01), serious intestinal injury (including intestinal villi atrophy and rupture, obvious infiltration of red blood cells and inflammatory cells), and enhanced iNOS expression in intestinal macrophages. Conventional treatment resulted in obviously longer survival time, but not significantly reduced intestinal permeability and pro-inflammatory cytokines, improved intestinal pathological structure, or expression of iNOS when compared with the rats in the sepsis group (P < 0.05, P < 0.01). In vitro experimental results showed that LPS stimulation induced the macrophages polarized to M1 phenotype, increased production of iNOS and TNF-α release (P < 0.01). DEX treatment significantly decreased iNOS expression and TNF-α level when compared with the cells of the LPS group (P < 0.05). Conclusion DEX protects the intestinal barrier function and attenuates intestinal injury in septic rats, which may be associated with its inhibition of M1 phenotype macrophage and inflammatory response.
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